《Table 1 Characteristics of MCP-1-transgenic mice》

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《The chemokine MCP-1(CCL2) in the host interaction with cancer: a foe or ally》

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Abbreviations:CNS，central nervous system；DNFB，2，4-dinitro-1-fluorobenzene；Lck，lymphocyte cell-specific protein tyrosine kinase；MBP，myelin basic protein；MMTV，mouse mammary tumor virus long terminal repeat.

The in vivo function of MCP-1 was further examined in five MCP-1 transgenic mouse models（Table 1）.36–40In a model in which MCP-1 was expressed in the epidermis（model 1）or several organs at high levels（model 2），no monocyte infiltrates were observed in MCP-1-expressing organs.Instead，the numbers of dendritic cells and Langerhans cells were increased in model 1.By contrast，in models 3，4 and 5，in which MCP-1expression was targeted to a specific organ，such as the thymus or central nervous system（model 3），type II alveolar epithelial cells in the lung（model 4）or pancreatic islets（model 5），respectively，monocyte infiltration was detected at MCP-1-producing sites；however，there was no sign of monocyte activation or tissue damage associated with the activation of monocytes.Interestingly，additional phenotypes were observed when mice were given exogenous stimuli.Contact hypersensitivity reactions to 2，4-dinitro-1-fluorobenzene were enhanced in the skin（model 1），and inflammatory responses in the lung upon intravenous（i.v.）injection of LPS or yeast wall glucan were also enhanced（model 4）.When model 5 mice were crossed with model 2 mice，the resulting mice showed no monocyte infiltration，indicating that high systemic MCP-1levels could prevent blood monocytes from responding to locally produced MCP-1.From these observations，it can be concluded that blood monocytes infiltrate tissues in response to local production，perhaps a low level of MCP-1，and then differentiate into macrophages in loco.However，their fate，whether they become immune-activating（M1）or suppressing（M2）macrophages，is likely determined by other mediators present at the sites.